CN104997942A - Traditional Chinese medicine for treating children's functional constipation caused by dyspepsia and internal heat - Google Patents

Abstract

The invention belongs to the technical field of medicines and particularly relates to a traditional Chinese medicine for treating children's functional constipation caused by dyspepsia and internal heat. The traditional Chinese medicine comprises the following crude drugs in parts by weight: 4-8 parts of coleseed, 2-4 parts of agilawood, 2-4 parts of buckwheat, 2-4 parts of endothelium corneum gigeriae galli, 2-4 parts of linseed, 2-4 parts of black sesame, 2-4 parts of begonia taiwaniana hayata, 2-4 parts of root tuber of phlomis betonicoides, 2-4 parts of polygonum multiflorum, 2-4 parts of semen cassiae and 2-4 parts of fruits of bothrocaryum controversum. The traditional Chinese medicine is used for treating children's functional constipation caused by dyspepsia and internal heat and has the advantages of high cure rate and total effective rate and excellent long-term curative effect.

Description

A kind of Chinese medicine for the treatment of pattern of fever Functional Constipation in Children in food stagnation

Technical field

The invention belongs to medical art, be specifically related to a kind of Chinese medicine for the treatment of pattern of fever Functional Constipation in Children in food stagnation.

Background technology

Functional constipation refers to that infant and child are because diet structure is unreasonable or lack difficult defecation caused by normal bowl evacuation habit, alteration of intestinal flora and colon, rectum, anus dyskinesis, account for infantile constipation more than 90%.Constipation is the disorderly symptom of the modal digestive tract function of children's, and main manifestations is: defecation frequency reduces, and the more important thing is that feces is hard, discharges difficulty.During defecation, anus has pain, and severe patient can cause anal fissure, hemorrhoid and proctoptosis.Sometimes a small amount of blood of excrement block surface attachment or mucus is made due to feces scratch intestinal mucosa.Functional constipation and organic constipation can be divided into by with or without organic disease.Along with the development of growth in the living standard and medical and health care system, the understanding that people endanger for constipation is also deepened gradually, with the passing of time the dyspepsia phenomenon such as lethargy, abdominal distention, dizziness, loss of appetite, sleep disorder can be there is in infant constipation, individually earn because exerting time just and easily cause proctoptosis, anal fissure or bring out the pathological changes such as hernia, the serious growth promoter that have impact on child and physical and mental health.

Infantile constipation is common with excess syndrome, heat syndrome.Because children's is " pure-yang constituent ", internal organs are tender and lovely, and shape gas does not fill, once ill mostly empirical, heat syndrome." side of declaring opinion children's door " is pointed out: " the pure sun of children's patient, overabundant heat is cold less also "." Yizong Jinjian pediatrics heart method ": " husband's breast and food, children's's money with foster survivor also.Stomach master receives and is subject to ... if father and mother cross love ... then dyspepsia does not disappear and disease one-tenth ".As can be seen here, infantile constipation is how weak by taste, eating and drinking without temperance, and hungry full uncomfortable, impairing the spleen and stomach, causes dyspepsia not changed, interior colon stomach, and FU QI being obstructed, or turbid QI failing to descend, fire-heat fumigating upward cardiopulmonary, move down caused by large intestine.This type sees children's, is referred to as " food stagnation interior-heat ".In the constipation of children's, this type is the most common.

Being used for treatment Functional Constipation in Children in clinical commonly uses bowel relieving relieving constipation, and QI flow promoting is pattern of fever Functional Constipation in Children in main treatment food stagnation, and applicant finds that this is not so good according to this Therapeutic Principle's clinical therapeutic efficacy, cure rate and aggregate efficiency on the low side.

Summary of the invention

Technical problem to be solved by this invention avoids the weak point existing for above-mentioned prior art, and provide a kind of Chinese medicine for the treatment of pattern of fever Functional Constipation in Children in food stagnation, it is high that this Chinese medicine has cure rate, and total effective rate is high, the advantage that late result is good.

The present invention is achieved through the following technical solutions:

Treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, be made up of the Chinese medicine of following weight portion:

Coleseed 4-8 part, Lignum Aquilariae Resinatum 2-4 part, Semen Fagopyri Esculenti 2-4 part, Endothelium Corneum Gigeriae Galli 2-4 part, Semen Lini 2-4 part, Semen Sesami Nigrum 2-4 part, Taiwan Caulis et folium euphorbiae milii 2-4 part, pungent ginseng 2-4 part, Radix Polygoni Multiflori 2-4 part, Semen Cassiae 2-4 part, Cornus controversa fruit 2-4 part.

Preferably, the Chinese medicine of pattern of fever Functional Constipation in Children in above-mentioned treatment food stagnation, is made up of the Chinese medicine of following weight portion:

Coleseed 5-7 part, Lignum Aquilariae Resinatum 2.5-3.5 part, Semen Fagopyri Esculenti 2.5-3.5 part, Endothelium Corneum Gigeriae Galli 2.5-3.5 part, Semen Lini 2.5-3.5 part, Semen Sesami Nigrum 2.5-3.5 part, Taiwan Caulis et folium euphorbiae milii 2.5-3.5 part, pungent ginseng 2.5-3.5 part, Radix Polygoni Multiflori 2.5-3.5 part, Semen Cassiae 2.5-3.5 part, Cornus controversa fruit 2.5-3.5 part.

Preferred, the Chinese medicine of pattern of fever Functional Constipation in Children in above-mentioned treatment food stagnation, is made up of the Chinese medicine of following weight portion:

Coleseed 6 parts, Lignum Aquilariae Resinatum 3 parts, 3 parts, Semen Fagopyri Esculenti, Endothelium Corneum Gigeriae Galli 3 parts, Semen Lini 3 parts, Semen Sesami Nigrum 3 parts, Taiwan Caulis et folium euphorbiae milii 3 parts, pungent ginseng 3 parts, Radix Polygoni Multiflori 3 parts, Semen Cassiae 3 parts, Cornus controversa fruit 3 parts.

The ratio of above weight proportion is through that science screening obtains, and for especial patient, as serious symptom or mild, fat or modest patient, can the proportioning of amount of corresponding adjustment composition, and increase or reduce being no more than 100%, drug effect is substantially constant.

The weight portion of said medicine, if in units of g, the normally consumption of 1 dose.

The indication of Chinese medicine of the present invention: be used for the treatment of pattern of fever Functional Constipation in Children in food stagnation.

The taboo item of Chinese medicine of the present invention: the fasting for the treatment of period in a medicine is greasy, raw and cold, the smelling of fish or mutton, irritant and stodgy food.

In each crude drug of Chinese medicine of the present invention,

Coleseed another name Semen Brassicae Campestris is the seed of crucifer Brassica campestris L BrassicacampestrisL..Pungent; Sweet; Flat.Return through liver; Kidney channel.Function blood circulation promoting and blood stasis dispelling; Dispersing swelling and dissipating binds; Loosening bowel to relieve constipation.Main prolonged lochia; Abdominal pain due to blood stasis; Dysmenorrhea; Discharging fresh blood stool; Dysentery; Fengshi Guanjie swells and ache; Carbuncle erysipelas; Acute mastitis; Constipation; Adhesive ileus.

Semen Fagopyri Esculenti another name flower wheat, Wu Mai; Hua Qiao, sweet buckwheat, buckwheat, triangle wheat are polygonaceae plant Semen Fagopyri Esculenti FagopyrumesculentumMoench [F.sagit-tatumGilib.; PolygonumfagopyrumL.] seed.Sweet; Micro-acid; Cold in nature.Return spleen; Stomach; Large intestine channel.Function spleen invigorating removing food stagnancy; The wide intestinal of the therapeutic method to keep the adverse QI flowing downwards; Removing toxic substances sore.Main the intestines and stomach stagnates; Have loose bowels; Dysentery; Strand intestinal cancer; White sand; Leukorrhagia; Spontaneous perspiration; Night sweat; Herpes; Erysipelas.

The native Radix Glycyrrhizae of pungent ginseng another name, white Radix Scrophulariae, west ginseng, Ramulus et Folium Mussaendae Pubescentis, white Radix Panacis Quinquefolii, white Radix Scrophulariae are the tuber of false Radix Gentianae Macrophyllae PhlomisbetonicoidesDiels [P.tuberosaauct.nonL.] of labiate.Sweet in the mouth; Bitter; Cool in nature.Function regulating qi-flowing for strengthening spleen; Removing toxic substances and promoting subsidence of swelling.Main dyspepsia; Abdominal distention; Diarrhoea; Cough with asthma breast is vexed; Flu; Laryngopharynx swelling and pain; Drug intoxication; Traumatic injury congestive edema

Taiwan Caulis et folium euphorbiae milii derives from Rosaceae Taiwan Caulis et folium euphorbiae milii MalustaiwanianaKaw.etKoidz., is used as medicine with fruit.Sweet, sour, puckery, tepor.Function regulating qi-flowing for strengthening spleen, dyspepsia and intestinal stasis relieving.Control food stagnation to stagnate, distension and fullness of the chest and abdomen pain.

Cornus controversa fruit is the fruit of Cornaceae plant Cornus controversa Bothrocaryumcontrouersa (Hemsl.) Poyark..Bitter in the mouth; Cool in nature.Function heat-clearing and toxic substances removing; Loosening bowel to relieve constipation; Drive ascarid.Main hepatitis; Dryness of the intestine constipation; Ascariasis.

Other raw material of Chinese medicine medicine is the Chinese medicine recorded in Chinese Pharmacopoeia 2010 editions.

The weak liver-yang hyperactivity of spleen, wood subjugates earth position be food stagnation of child interior-heat commonly encountered diseases because of, its theoretical foundation derives from " the liver being liable to excess, the spleen tending to insufficiency usually "." the liver being liable to excess " is not detected in children's's movability liver-wind and frver convulsions etc., also sees the easy emotional instability of children's, irascible temperament, because of liver not only main air, and also main feelings will and catharsis.In addition modern city children's majority is spoilt, and has formed wilful, irritable habit, has been more prone to increase the weight of " the liver being liable to excess " this pathological phenomenon.And The spleen has the function to transport and transform nutrients, children's's " the spleen tending to insufficiency usually " then easy being affected by fluid-retention food and occur digestion, absorb and the exception of excretion aspect.The two common pathogenetic, defines the situation of " the weak liver-yang hyperactivity of spleen ", edema with the liver involved gram spleen soil, excessively rises the irritability sent out and restrains spleen soil, infant is occurred constipation, have a bad temper, diet difference series of symptoms.Face inspection eye born of the same parents pastiness is the typical case of wood subjugates earth position.So treatment infantile constipation should focus on spleen invigorating suppressing the hyperactive liver, dredge it and have a surplus and tonifying for deficiency syndrome.

The prescription mechanism of Chinese medicine of the present invention is as follows:

We are monarch drug with coleseed, Lignum Aquilariae Resinatum, and two medicines one enter edema caused by disorder of QI, and one enters blood system; One invigorates blood circulation, a circulation of qi promoting; One intestine moistening, a removing food stagnancy; Embody the method for the treatment of principle of we.Semen Fagopyri Esculenti, Endothelium Corneum Gigeriae Galli, Semen Lini, Semen Sesami Nigrum four medicine are minister: Semen Fagopyri Esculenti and Endothelium Corneum Gigeriae Galli compatibility can dyspepsia and intestinal stasis relieving, promote the discharge of gastrointestinal retention; Endothelium Corneum Gigeriae Galli and Semen Lini match can promoting blood circulation, removing blood stasis and relieving pain, promotes gastrointestinal peristalsis, and can the stomachache that causes of constipation relieving abdominal distention; Semen Lini and Semen Sesami Nigrum match loosening bowel to relieve constipation; Above four medicines can help digestion intestine moistening, again can blood circulation promoting regulates qi, and at this auxiliary monarch drug jointly, make to tie in the intestines and stomach in heat and food, the pathological state of large intestine conduction transportation capabilities dereliction of duty is improved.Help with Taiwan Caulis et folium euphorbiae milii, Xin Can, Radix Polygoni Multiflori, Semen Cassiae, Cornus controversa fruit, Taiwan Caulis et folium euphorbiae milii, pungent ginseng are that assistant helps again: assistant principal drug assistance ministerial drug is strengthened regulating the flow of vital energy the merit of intestinal stasis relieving; Radix Polygoni Multiflori, Semen Cassiae, Cornus controversa fruit is assistant system: this three tastes flavour of a drug bitterness is trembled with fear, and both can help the hot medicine in monarch processed, ministerial drug, again can heat clearing away YIN nourishing, moistening dryness for relaxing bowels.

We embody and control gas, control blood, control long-pending, to control heat feature in a word, make gas promoting the circulation of blood smooth, and long-pending disappearing just is led to.Both can lead to it just, just not damage it again, make deficient dirtyly to be recovered.

Detailed description of the invention

Below in conjunction with specific embodiment, the present invention is further described, so that those skilled in the art more understands the present invention, but does not therefore limit the present invention.

Embodiment 1

Treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, each crude drug weight proportion is as follows:

Coleseed 6g, Lignum Aquilariae Resinatum 3g, Semen Fagopyri Esculenti 3g, Endothelium Corneum Gigeriae Galli 3g, Semen Lini 3g, Semen Sesami Nigrum 3g, Taiwan Caulis et folium euphorbiae milii 3g, pungent ginseng 3g, Radix Polygoni Multiflori 3g, Semen Cassiae 3g, Cornus controversa fruit 3g.

Embodiment 2

Treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, each crude drug weight proportion is as follows:

Coleseed 5g, Lignum Aquilariae Resinatum 2.5g, Semen Fagopyri Esculenti 3.5g, Endothelium Corneum Gigeriae Galli 2.5g, Semen Lini 3.5g, Semen Sesami Nigrum 2.5g, Taiwan Caulis et folium euphorbiae milii 3.5g, pungent ginseng 2.5g, Radix Polygoni Multiflori 3.5g, Semen Cassiae 2.5g, Cornus controversa fruit 3.5g.

Embodiment 3

Treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, each crude drug weight proportion is as follows:

Coleseed 7g, Lignum Aquilariae Resinatum 3.5g, Semen Fagopyri Esculenti 2.5g, Endothelium Corneum Gigeriae Galli 3.5g, Semen Lini 2.5g, Semen Sesami Nigrum 3.5g, Taiwan Caulis et folium euphorbiae milii 2.5g, pungent ginseng 3.5g, Radix Polygoni Multiflori 2.5g, Semen Cassiae 3.5g, Cornus controversa fruit 2.5g.

Embodiment 4

Treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, each crude drug weight proportion is as follows:

Coleseed 4g, Lignum Aquilariae Resinatum 4g, Semen Fagopyri Esculenti 2g, Endothelium Corneum Gigeriae Galli 4g, Semen Lini 2g, Semen Sesami Nigrum 4g, Taiwan Caulis et folium euphorbiae milii 2g, pungent ginseng 4g, Radix Polygoni Multiflori 2g, Semen Cassiae 4g, Cornus controversa fruit 2g.

Embodiment 5

Treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, each crude drug weight proportion is as follows:

Coleseed 8g, Lignum Aquilariae Resinatum 2g, Semen Fagopyri Esculenti 4g, Endothelium Corneum Gigeriae Galli 2g, Semen Lini 4g, Semen Sesami Nigrum 2g, Taiwan Caulis et folium euphorbiae milii 4g, pungent ginseng 2g, Radix Polygoni Multiflori 4g, Semen Cassiae 2g, Cornus controversa fruit 4g.

Carried out clinical pharrnacokinetics test to Chinese medicine of the present invention, Details as Follows:

1. case selection standard

All cases all meet Chinese and western medicine diagnostic criteria and Standards of Chinese Medical Syndrome Differentiation, and through including exclusion standard screening eligible in.

1 data and method

1.1 clinical data

Choose this Out-patient Department constipation infant 6O example, be divided into treatment group and each 30 examples of matched group, wherein treatment group man 17 example at random, female 13 example; Age June ~ 3 years old 21 example, 4 ~ 9 years old 8 example, 1O ~ 14 year old 1 example; Course of disease 2w ~ 2 month 19 example, 2 ~ June 6 is routine, > 6 months 5 examples; 6 examples that the state of an illness is slight, moderate 21 example, severe 3 example.Matched group man 17 example, female 13 example; June ~ 3 years old 20 example, 4 ~ 9 years old 8 example, 10 ~ 14 years old 2 example; Course of disease 2w ~ 2 month 17 example, 2 ~ June 9 is routine, > 6 months 4 examples; 10 examples that the state of an illness is slight, moderate 18 example, severe 2 example.The physical data such as two groups of sexes, age, the course of disease, state of an illness compare, and no significant difference (P > 0.05), has comparability.

1.2 diagnostic criteria

Diagnosis meets the syndrome diagnostic criterion of heat syndrome and the Western medicine diagnose standard person of constipation in children in the tcm diagnosis standard of constipation in children, constipation food stagnation and can include in.

1.2.1 the diagnostic point of the middle infantile constipation of diagnostic criteria reference " Chinese medical disease Standardization of diagnosis and curative effect " of traditional Chinese medical science constipation: 1) not think breast food, eat without digesting, abdominal part distension, constipation with dry stool is feature; 2) with crying and screaming at dysphoria, night or the disease such as vomiting; 3) dyspepsia due to improper feeding history is had; 4) the visible indigestion food debris of feces examination and fat drop.Infant need at least possess the 1st) item.

1.2.2 in traditional Chinese medical science constipation food stagnation, the syndrome diagnostic criterion of heat syndrome is with reference to " Chinese medical disease Standardization of diagnosis and curative effect ", and the syndrome diagnostic criterion of heat syndrome in constipation food stagnation: 1) constipation with dry stool, discharges difficulty; 2) red tongue or red deep red, tongue fur BOHUANG, Huang are greasy or yellow thick greasy; 3) deep and forceful pulse or cunning, fingerprint purple is stagnant; 4) flushed complexion fever of the body, red lip, halitosis; 5) abdominal distention or stomachache is accompanied, uneasy sleeping at night; 6) inappetence, stomach poor appetite is few; 7) yellowish or reddish urine.Infant need possess 1) ~ 3) item and 4) ~ 7) in item 2.

1.2.3 the diagnostic criteria of doctor trained in Western medicine constipation is with reference to " all good fortune Chinese bush cherry practical paidonosologies " and constipation Rome Ⅲ criteria: 1) infrequent defecation natural law > 2d, defecation frequency < 3 times/w when not using cathartic; 2) be hard and dry hard and/or have difficult defecation; 3) course of disease >=2w.Infant need possess above 3 simultaneously.

1.3 test method

1.3.1 treatment group give the embodiment of the present invention 1 treatment food stagnation in the Chinese medicine of pattern of fever Functional Constipation in Children, every day 1 dose, add water 500ml, decocts into 100ml.Be decocted in water for oral dose, 1 dose/d.

1.3.2 matched group selects WANGSHI BAOCHI WAN, usage and dosage Consult drug description.

1.3.3 time point 1 is observed) course for the treatment of is 2w, observes 1 course for the treatment of, when treatment 1,2w, record is marked respectively.2) 2w is followed up a case by regular visits to.

1.3.4 observation index feces character, defecation time, appetite behavior, abdominal pain and distension situation, urine color, lip color, picture of the tongue and pulse condition etc.

1.4 the standard of curative effect evaluation

Reference " Chinese medical disease Standardization of diagnosis and curative effect " is also formulated in conjunction with clinical practice: 1) clinical recovery: stool is normal, and remaining symptom disappears (deduction rate >=95) substantially; 2) effective: constipation situation is obviously improved, remaining symptom major part disappears (deduction rate >=70); 3) effective: infrequent defecation shortens and/or just matter makes moderate progress, and remaining symptom all take a favorable turn (deduction rate >=3O); 4) invalid: symptomatology is almost without improving (deduction rate < 30).Symptom integral deduction rate computational methods: deduction rate=[before (before treatment the rear integration of integration-treatment)/treatment integration] × 100.

1.5 statistical method

Adopt SPSS17.0 statistical software to carry out data analysis, enumeration data rate represents, adopts inspection, with P < 0.05 for difference has statistical significance.

2 results

Comparitive study during 2.1 liang of group treatment 1W

During treatment 1W, the cure rate for the treatment of group is 20.00%, total effective rate is 83.3%, matched group is cure rate is 3.33%, total effective rate is that there were significant differences (P < 0.01 and P < 0.05) (see table 1) for 70.00%, two groups of cure rates and total effective rate.

Table 1 liang is organized comparitive study when treating 1W and is analyzed

Group	n	Recovery from illness	Effective	Effectively	Invalid	Cure rate (%)	Total effective rate (%)
								Treatment group	30	6	16	3	5	20.00**	83.33*
Matched group	30	1	8	12	9	3.33	70.00

Compared with matched group, * P < 0.05; * P < 0.01.

Comparitive study during 2.2 liang of group treatment 2W

The cure rate for the treatment of group is 50.00%, total effective rate is 96.67%, matched group is cure rate is 20.00%, and total effective rate is that there were significant differences (P < 0.01 and P < 0.05) (see table 2) for 80.00%, two groups of cure rates and total effective rate.

Table 2 liang is organized comparitive study when treating 2W and is analyzed

Group	n	Recovery from illness	Effective	Effectively	Invalid	Cure rate (%)	Total effective rate (%)
								Treatment group	30	15	10	4	1	50.00**	96.67*
Matched group	30	5	12	8	5	20.00	80.00

Compared with matched group, * P < 0.05; * P < 0.01.

The treatment of 2.3 liang of groups terminates rear 2W and follows up a case by regular visits to comparitive study

After two groups of courses for the treatment of terminate, follow up a case by regular visits to 2w, the cure rate for the treatment of group is 60.00%, total effective rate is 96.67%, matched group is cure rate is 20.00%, total effective rate is that 76.67%, two groups of cure rates and total effective rate have pole significant difference (P < 0.01) (see table 3), shows that this Chinese medicine late result of the present invention is better than WANGSHI BAOCHI WAN.

A table 3 liang group treatment terminates rear 2w and follows up a case by regular visits to comparitive study analysis

Group	n	Recovery from illness	Effective	Effectively	Invalid	Cure rate (%)	Total effective rate (%)
								Treatment group	30	18	10	1	1	60.00**	96.67**
Matched group	30	5	8	10	7	20.00	76.67

Compared with matched group, * * P < 0.01.

2.4 untoward reaction

Obvious adverse reaction and drug allergy person is not there is in therapeutic process.

Claims (3)

1. treat a Chinese medicine for pattern of fever Functional Constipation in Children in food stagnation, be made up of the Chinese medicine of following weight portion:

Coleseed 4-8 part, Lignum Aquilariae Resinatum 2-4 part, Semen Fagopyri Esculenti 2-4 part, Endothelium Corneum Gigeriae Galli 2-4 part, Semen Lini 2-4 part, Semen Sesami Nigrum 2-4 part, Taiwan Caulis et folium euphorbiae milii 2-4 part, pungent ginseng 2-4 part, Radix Polygoni Multiflori 2-4 part, Semen Cassiae 2-4 part, Cornus controversa fruit 2-4 part.

2. the Chinese medicine of pattern of fever Functional Constipation in Children in treatment food stagnation according to claim 1, is characterized in that, be made up of the Chinese medicine of following weight portion:

Coleseed 5-7 part, Lignum Aquilariae Resinatum 2.5-3.5 part, Semen Fagopyri Esculenti 2.5-3.5 part, Endothelium Corneum Gigeriae Galli 2.5-3.5 part, Semen Lini 2.5-3.5 part, Semen Sesami Nigrum 2.5-3.5 part, Taiwan Caulis et folium euphorbiae milii 2.5-3.5 part, pungent ginseng 2.5-3.5 part, Radix Polygoni Multiflori 2.5-3.5 part, Semen Cassiae 2.5-3.5 part, Cornus controversa fruit 2.5-3.5 part.

3. the Chinese medicine of pattern of fever Functional Constipation in Children in treatment food stagnation according to claim 3, is characterized in that, be made up of the Chinese medicine of following weight portion:

Coleseed 6 parts, Lignum Aquilariae Resinatum 3 parts, 3 parts, Semen Fagopyri Esculenti, Endothelium Corneum Gigeriae Galli 3 parts, Semen Lini 3 parts, Semen Sesami Nigrum 3 parts, Taiwan Caulis et folium euphorbiae milii 3 parts, pungent ginseng 3 parts, Radix Polygoni Multiflori 3 parts, Semen Cassiae 3 parts, Cornus controversa fruit 3 parts.